Racial disparity in the clinical outcomes of HER2-low and HER2-zero early-stage breast cancer.

Shipra Gandhi Roswell Park Comprehensive Cancer Center, Buffalo, NY info_outline Shipra Gandhi, Kayla Catalfamo, Kristopher Attwood, Ankita Kapoor, Karan Jatwani, Arya Mariam Roy

Authors Shipra Gandhi Roswell Park Comprehensive Cancer Center, Buffalo, NY info_outline Shipra Gandhi, Kayla Catalfamo, Kristopher Attwood, Ankita Kapoor, Karan Jatwani, Arya Mariam Roy Organizations Roswell Park Comprehensive Cancer Center, Buffalo, NY Abstract Disclosures Research Funding No funding received None. Background: The expansion of the spectrum of HER2 breast cancer (BC) to include HER2-low status has had major impact in oncology. More than half of the BC patients (pts) are now categorized as HER2-low. With the recent approval of antibody-drug conjugates in HER2-low BC, HER2-low has emerged as a distinct targetable entity. BC pts who attain pCR after neoadjuvant chemotherapy (NAC) have a better prognosis. We analyzed the association of race with attainment of pCR among HER2-low and HER2-zero pts treated with NAC and with survival. Methods: We queried the National Cancer Database for stage I, II, III BC pts who received NAC from 2010 – 2019. The population was divided into two cohorts: HER2-low and HER2-zero. All associations were compared using Kruskal-Wallis, Pearson’s Chi-Squared, and Fisher’s Exact Tests. Multivariate cox regression models were generated for overall survival (OS) adjusted for age, race, stage, grade, body mass index, treatments, subtypes, insurance and comorbidities. Results: A total of 72,279 pts was included in the analysis (HER2-zero = 71,091, HER2-low = 1,188). There was higher hormone receptor (HR)-positivity in HER2-low vs. HER2-zero groups (69% vs 54%, p < 0.001). Higher percentage of pts had private insurance in the HER2- low group (60% vs 4%, p < 0.001). Race, age, clinical T and N-staging were distributed equally between both cohorts. Among all races, those with HER2-low status had lower pCR compared to HER2-zero, but this was not statistically significant. The rate of pCR was similar across racial groups in both HER2-low and HER2-zero groups, though was not statistically significant. In the HER2-zero group, Blacks had worse while Asians had better survival compared to Caucasians in overall (Blacks: hazard ratio (HR) 1.36, 95% CI = 1.3-1.4; Asians: HR 0.60, 95% CI = 0.57-0.74), HR-positive (Blacks: HR 1.4, 95% CI = 1.3-1.4; Asians: HR 0.60, 95% CI = 0.53-0.75) and HR-negative (Blacks: HR 1.2, 95% CI = 1.17-1.29; Asians: HR 0.69, 95% CI = 0.58-0.83) subtypes (all p < 0.001). However, this racial disparity in survival was not observed in the HER2-low group in the overall population (Blacks: HR 1.1, 95% CI = 0.7-1.5, p = 0.5; Asians: HR 0.38, 95% CI = 0.14-1.03, p = 0.06) or within subtypes. Interestingly, among Blacks, pts with HER2-zero disease had worse survival compared to HER2-low disease (5-yr OS: 73% vs 81%, p = 0.02, HR 1.4, 95% CI = 1.05-1.9, p = 0.02). This survival difference was not observed in any other races. Conclusions: Racial disparity in survival plays a role in the HER2-zero, not in HER2-low early-stage BC. Blacks who received NAC have decreased OS in the HER2-zero group, not in HER2-low group compared to other races. More studies are needed to confirm this finding and identify the mechanism underlying this disparity. Among Blacks, those with HER2-zero BC had worse survival compared to HER2-low. This highlights the need for personalized treatment options for Blacks for HER2-zero BC.